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Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Endotoxin immunity and the development of the systemic inflammatory response syndrome in critically ill children
R C M Stephens1, K Fidler2, P Wilson3
1Critical Care Group, Portex Unit, Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK. r.stephens@ich.ucl.ac.uk.
Insights
Children with lower endotoxin core antibodies (EndoCAb) are more likely to develop systemic inflammatory response syndrome (SIRS) after non-infectious ICU admissions. This suggests EndoCAb may protect against SIRS in post-operative and head-injured pediatric patients.
Area of Science:
- Pediatric Intensive Care
- Immunology
- Critical Care Medicine
Background:
- Systemic inflammatory response syndrome (SIRS) can be triggered by endotoxin.
- Endotoxin core antibodies (EndoCAb) are protective in sepsis and post-surgery.
- Previous research suggests a link between EndoCAb and patient outcomes.
Purpose of the Study:
- To investigate the relationship between endotoxin core antibodies (EndoCAb) and the development of SIRS in pediatric intensive care unit (PICU) patients.
- To determine if EndoCAb levels differ in patients who develop SIRS versus those who do not, stratified by infection status.
Main Methods:
- 139 pediatric patients with multiple organ failure were recruited.
- Patients were categorized by infectious or non-infectious diagnosis upon PICU admission.
- Serum IgG EndoCAb levels were measured and correlated with SIRS development within 48 hours, alongside C-reactive protein and mannose-binding lectin.
Main Results:
- In non-infectious cases (post-operative, head injury), significantly lower IgG EndoCAb levels were observed in patients who developed SIRS (72 MU/ml) compared to those who did not (131 MU/ml).
- In infectious cases, no significant difference in IgG EndoCAb levels was found between patients who developed SIRS and those who did not.
- These findings were independent of confounding variables like C-reactive protein and mannose-binding lectin.
Conclusions:
- Pediatric patients with head injuries or post-operative conditions admitted to the PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels.
- EndoCAb may play a protective role against SIRS in specific pediatric patient populations, particularly those without infection.
Background:
The systemic inflammatory response syndrome (SIRS) may be triggered by endotoxin. Humans have antibodies directed against the core of endotoxin (endotoxin core antibodies, EndoCAb) that appear to be protective following surgery and in sepsis. We hypothesised that children with elevated antibodies to endotoxin core would be less likely to develop SIRS in their initial period on intensive care. Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection.
Methods:
We recruited 139 consecutive patients admitted to a paediatric intensive care unit (PICU) with more than one organ failure for longer than 12 h as part of another study. Patients were classified on admission to PICU as having an infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of admission was recorded along with detailed clinical and demographic data, EndoCAb concentration and the potential confounding variables C-reactive protein and mannose-binding lectin.
Results:
In the 71 patients admitted without infection (primarily post-operative and head injured) IgG EndoCAb was significantly lower in patients who developed SIRS than those who did not (72 vs. 131 MU/ml), independent of potential confounding variables. In patients with infection there was no significant difference in IgG EndoCAb between children developing SIRS and those who did not (111 vs. 80 MU/ml).
Conclusion:
Head injured and post-operative patients admitted to PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels than those who do not.
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